Migration Inhibitory Factor Concentrations Research Articles

Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis

Background & AimsMacrophage migration inhibitory factor (MIF) is an inflammatory cytokine and an important regulator of innate immune responses. We hypothesised that serum concentrations of MIF are associated with disease severity and outcome in patients with decompensated cirrhosis and acute-on-chronic liver failure (ACLF).MethodsCirculating concentrations of MIF and its soluble receptor CD74 (sCD74) were determined in sera from 292 patients with acute decompensation of cirrhosis defined as new onset or worsening of ascites requiring hospitalisation. Of those, 78 (27%) had ACLF. Short-term mortality was assessed 90 days after inclusion.ResultsAlthough serum concentrations of MIF and sCD74 did not correlate with liver function parameters or ACLF, higher MIF (optimum cut-off >2.3 ng/ml) and lower concentrations of sCD74 (optimum cut-off <66.5 ng/ml) both indicated poorer 90-day transplant-free survival in univariate analyses (unadjusted hazard ratio [HR] 2.01 [1.26–3.22]; p = 0.004 for MIF; HR 0.59 [0.38–0.92]; p = 0.02 for sCD74) and after adjustment in multivariable models. Higher MIF concentrations correlated with surrogates of systemic inflammation (white blood cells, p = 0.005; C-reactive protein, p = 0.05) and were independent of genetic MIF promoter polymorphisms. Assessment of MIF plasma concentrations in portal venous blood and matched blood samples from the right atrium in a second cohort of patients undergoing transjugular intrahepatic portosystemic shunt insertion revealed a transhepatic MIF gradient with higher concentrations in the right atrial blood.ConclusionsSerum concentrations of MIF and its soluble receptor CD74 predict 90-day transplant-free survival in patients with acute decompensation of cirrhosis. This effect was independent of liver function and genetic predispositions, but rather reflected systemic inflammation. Therefore, MIF and sCD74 represent promising prognostic markers beyond classical scoring systems in patients at risk of ACLF.Lay summaryInflammatory processes contribute to the increased risk of death in patients with cirrhosis and ascites. We show that patients with high serum levels of the inflammatory cytokine macrophage migration inhibitory factor (MIF) alongside low levels of its binding receptor sCD74 in blood indicate an increased mortality risk in patients with ascites. The cirrhotic liver is a relevant source of elevated circulating MIF levels.

Expression profile of macrophage migration inhibitory factor in periodontitis

ObjectiveMacrophage migration inhibitory factor (MIF) is a pivotal mediator of host innate immunity and influences the development of several inflammatory diseases. The role of MIF in periodontitis is unclear. MethodsEighteen periodontally healthy volunteers and 18 patients with stage III or IV periodontitis were enrolled. Blood samples and gingival tissues were collected from all individuals. The serum concentrations of MIF and MCP-1 were measured by ELISA. The protein and mRNA levels of MIF and MCP-1 in gingival tissue were evaluated by immunohistochemical staining and quantitative PCR. The levels of secreted MIF and MCP-1, as well as their mRNA levels, were determined by ELISA and quantitative PCR in oral epithelial cells infected with Porphyromonas gingivalis. ResultsAfter adjusting for age, the level of MCP-1 was significantly higher in the serum and gingival tissue of periodontitis patients, as well as in infected epithelial cells. The serum concentration of MIF was increased in periodontitis patients (15.25 ± 2.16 ng/mL, P < 0.05) compared to healthy controls (10.43 ± 1.02 ng/mL). Increased MIF immunoreactivity was found in gingival epithelial tissue but not in the gingival connective tissue of periodontitis patients. The secretion of MIF was 3.82-fold higher in the supernatant of infected cells than in the supernatant of control (P < 0.01). No increase in the MIF mRNA level was found in either gingival tissue or epithelial cells. ConclusionsBased on our limited evidence, we showed the level of MIF was related to periodontal conditions. P. gingivalis may contribute to the development and progression of periodontitis through MIF.

Migration inhibitory factor in spinal tuberculosis: -173G/C polymorphisms, and transcript and protein levels in a northern province of China.

The aim of this study was to elucidate the possible association between migration inhibitory factor (MIF)-173G/C gene polymorphisms and transcript and plasma levels of MIF in spinal tuberculosis (TB) patients. Clinical data were collected from 254 spinal TB patients and 262 healthy controls participating in the study. The genotype of the MIF-173G/C gene was amplified by polymerase chain reaction and genotyped by DNA sequencing technology. The level of mRNA expression was determined by real-time polymerase chain reaction and MIF plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay. The frequency of the C allele and GC+CC genotype in MIF-173G/C was over-represented in spinal TB patients. The mean MIF mRNA level in spinal TB patients and patients with the GG and GC+CC genotype were significantly lower than controls; however, our study also indicated that the MIF concentration in spinal TB patients and patients with the GG and GC+CC genotypes were significantly higher than controls. Spinal TB patients with the GG genotype had higher MIF plasma levels than patients with the GC+CC genotype. The C-reactive protein level and erythrocyte sedimentation rate was correlated with the MIF plasma level. In summary, the association between the MIF-173G/C genetic polymorphism, reduced transcript and increased plasma levels of MIF in spinal TB patients, and MIF may play an important role in the occurrence, development, and damage of spinal TB in the northern Province population of China.

Macrophage migration inhibitory factor modulates proliferation, cell cycle, and apoptotic activity in head and neck cancer cell lines

Background/purposeMacrophage migration inhibitory factor (MIF) is a multifunctional cytokine that contributes to the progression of several cancers. MIF overexpression has been reported in head and neck squamous cell carcinoma (HNSCC) patients. However, the exact role of MIF in HNSCC is not fully understood. Our aim was to evaluate the amount of secreted MIF and the role of MIF in the proliferation, cell cycle, and apoptosis in HNSCC cell lines.Materials and methodsGenetically matched HNSCC cell lines derived from primary (HN18 and HN30) and metastatic sites (HN17 and HN31) from the same patient were used in this study. The MIF levels in conditioned media from the HNSCC cell lines were evaluated using ELISA. The HNSCC cell lines were treated with recombinant MIF at concentrations 25, 50 and 100 ng/ml, and cell proliferation was evaluated by MTT assay. A proliferative dose of MIF was used to treat the cells then, cell cycle, and apoptotic status were determined by flow cytometry.ResultsThe HNSCC-secreted MIF concentration ranged from 49.33 to 973 pg/ml. Exogenous MIF (25 ng/ml) significantly increased HN18, HN30, and HN31 cell proliferation. Moreover, MIF induced cell cycle progression and inhibited apoptosis in these cells. However, MIF did not affect growth or apoptosis in HN17 cell.ConclusionMIF secreted from the HNSCC cell lines were evaluated. Exogenous MIF promotes various effects on proliferation, cell cycle, and apoptosis in HNSCC cells.

Upregulation of MIF as a defense mechanism and a biomarker of Alzheimer\u2019s disease

BackgroundMacrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine. Chronic inflammation induced by amyloid β proteins (Aβ) is one prominent neuropathological feature in Alzheimer’s disease (AD) brain.MethodsElisa, Western blot, and immunohistochemical staining analysis were performed to examine the level of MIF protein in CSF and brain tissues. MTT and LDH assays were used to examine the neurotoxicity, and the Morris Water Maze test was performed to examine the cognitive function in the MIF+/−/APP23 transgenic mice.ResultsMIF expression was upregulated in the brain of AD patients and AD model mice. Elevated MIF concentration was detected in the cerebrospinal fluid of AD patients but not in that of the patients suffering from mild cognitive impairment and vascular dementia. Reduced MIF expression impaired learning and memory in the AD model mice. MIF expression largely associates with Aβ deposits and microglia. The binding assay revealed a direct association between MIF and Aβ oligomers. Neurons instead of glial cells were responsible for the secretion of MIF upon stimulation by Aβ oligomers. In addition, overexpression of MIF significantly protected neuronal cells from Aβ-induced cytotoxicity.ConclusionOur study suggests that neuronal secretion of MIF may serve as a defense mechanism to compensate for declined cognitive function in AD, and increased MIF level could be a potential AD biomarker.

Increased serum levels of macrophage migration inhibitory factor in autism spectrum disorders

ObjectiveMacrophage migration inhibitory factor (MIF) has been suggested as a pivotal regulator of innate immunity and inflammatory. The aim of this study was to measure serum circulating levels of MIF in relation to the degree of the severity of autism spectrum disorders (ASD). MethodsOne hundred and two Chinese children with ASD and same their age-sex matched typical development children were included. Concentrations of MIF were tested by Quantikine Human MIF Immunoassay. Serum levels of homocysteine (HCY), C-reactive protein (CRP) and serum Interleukin 6 (IL-6) were also tested. The influence of serum levels of MIF on ASD risk and ASD severity were performed by binary logistic regression analysis. ResultsThe serum levels of MIF in the children with ASD (24.7 ± 08.9 ng/ml) were significantly higher than those of control subjects (18.3 ± 5.5 ng/ml) (t = 6.134, P < 0.001). Levels of MIF increased with increasing severity of ASD as defined by the CARS score (P < 0.001). In multivariate model, MIF was associated with an increased risk of ASD (OR 1.11, 95% CI: 1.05–1.17; P < 0.001). MIF improved the combined model (HCY/CRP/IL-6) to predict ASD (P < 0.001). At admission, 68 children (66.7%) had a severe autism. In these children, the mean serum level of MIF was higher than in those children with mild to moderate autism (28.1 ± 8.5 ng/ml VS. 17.9 ± 4.7 ng/ml; t = 6.482, P < 0.001). In multivariate model, MIF was still associated with an increased risk of severe ASD (OR: 1.15, 95% CI: 1.04–1.19; P < 0.001). MIF improved the combined model (HCY/CRP/IL-6) to predict severe ASD (P < 0.001). ConclusionsThese results identify high serum MIF levels are associated with severity of ASD. Further study is warranted on the precise involvement of MIF in ASD, and the mechanism by which MIF contributes to ASD pathogenesis.

Elevated plasma macrophage migration inhibitor factor as a risk factor for the development of post-stroke depression in ischemic stroke

BackgroundMacrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity and inflammatory responses, has been reported to link to the pathophysiology of cardiovascular disease and depression. The aim of this study was to test the possible association between plasma MIF and the development of post-stroke depression (PSD) in Chinese patients with acute ischemic stroke (AIS). MethodsThe first-ever AIS patients who were hospitalized at Affiliated Hospital of Weifang Medical College during the period from November 2015 to September 2017 were included. Neurological and neuropsychological evaluations were conducted at the 3-month follow-up. Plasma concentrations of MIF were tested by Quantikine Human MIF Immunoassay. Plasma levels of homocysteine (HCY), C-reactive protein (CRP) and Interleukin 6 (IL-6) were also tested. Results were expressed as percentages for categorical variables and as medians (Interquartile range-IQR) for the continuous variables. ResultsFinally, 333 stroke patients were included, and 95 out of those patients (28.5%) were classified as major depression. In the patients with major depression, plasma levels of MIF were higher compared with those in patients free-depression [27.3(IQR, 23.5–34.9) ng/ml vs. 20.9(IQR, 17.0–24.8) ng/ml; Z = 8.369, P < 0.001]. For each 1unit increase of MIF, the unadjusted and adjusted risk of PSD increased by 18% (odds ratios [OR]: 1.18; 95% confidence interval [CI], 1.13–1.23, P < 0.001) and 11% (1.11; 1.02–1.16, P = 0.001), respectively. In a multivariate model using the elevated levels of MIF (≥median) vs. normal (<median) together with the other significant clinical variables, the marker displayed prognostic information (PSD: OR for fourth quartile, 3.05 [95% CI, 1.65–6.11; P < 0.001]). When MIF was added to the model containing established significant risk factors, Area Under the Receiver Operating Characteristic curve (AUROC; standard error) was increased from 0.81(0.025) to 0.86(0.019). A significant difference in the AUROC between the established risk factors alone and the addition of MIF was observed (difference, 0.05[0.006]; P = 0.004). ConclusionThe present study demonstrated that elevated plasma levels of MIF at admission were associated with increased risk of PSD in the next three months and might be useful in identifying stroke at risk for PSD for early prevention strategies.

Macrophage migration inhibitory factor as a serum prognostic marker in patients with aneurysmal subarachnoid hemorrhage

BackgroundMacrophage migration inhibitory factor (MIF) has been implicated in inflammation. We clarified whether serum MIF could be used as a marker of inflammation, brain damage and outcome after aneurysmal subarachnoid hemorrhage (aSAH). MethodsSerum samples from 102 aSAH adults and 102 healthy controls were determined. The World Federation of Neurological Surgeons (WFNS) scale was used for neurological evaluation and radiological severity was estimated in accordance with the Fisher scale. ResultsSerum MIF, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and S100B concentrations were significantly higher in patients than in controls. Serum MIF concentrations correlated with WFNS scores and Fisher scores and serum concentrations of CRP, IL-6, TNF-α and S100B. Serum MIF was identified as an independent predictor for 6-month unfavorable outcome (defined as Extended Glasgow Outcome Scale score of 1–4). Area under receiver operating characteristic curve of serum MIF concentrations was similar to those of WFNS scores, Fisher scores and serum S100B concentrations and significantly exceeded those of serum CRP, IL-6 and TNF-α concentrations. ConclusionsSerum MIF provides information about inflammation, brain injury severity and outcome after aSAH, which can be useful as a complement to clinical data.

Serum macrophage migration inhibitory factor concentrations correlate with prognosis of traumatic brain injury

BackgroundMacrophage migration inhibitory factor (MIF) is a well-known pro-inflammatory cytokine. Serum MIF concentrations are associated with the severity and prognosis of ischemic stroke. MethodsIn this prospective, observational study, white blood cell (WBC) count and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and MIF among 108 severe traumatic brain injury (TBI) patients and 108 controls were measured. We determined whether serum MIF concentrations are associated with inflammation, severity, in-hospital major adverse events (IMAEs) (i.e., in-hospital mortality, acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury and posttraumatic cerebral infarction) and long-term clinical outcome (i.e., 6-month functional outcome) after TBI. ResultsAs compared to the controls, serum CRP, IL-6, TNF-α and MIF concentrations were significantly increased. MIF concentrations correlated with WBC count, CRP, IL-6 and TNF-α concentrations and Glasgow coma scale (GCS) scores. MIF in serum was independently associated with IMAEs and long-term clinical outcome. Area under receiver operating characteristic curve of MIF concentrations was similar to GCS scores'. Moreover, MIF concentrations markedly improved the predictive value of GCS scores for 6-month unfavorable outcome. ConclusionIncreased serum MIF concentrations have close relation to inflammation, trauma severity and clinical outcomes, substantializing MIF as a good prognostic biomarker after TBI.

Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease

BACKGROUND:To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome.MATERIALS/METHODS:We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35).RESULTS:We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups.DISCUSSION:The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process.

GW24-e0805 Mesenchymal Stem Cells down-regulates MIF expression on myocardium in septic mice

ObjectivesAs a novel anti-inflammationary and immuno-regulatory factor, Mesenchymal Stem Cells (MSCs) have recently been applied to treat septic animals in experimental research. Our previous results have shown that MSCs decreased...

Evaluation of Macrophage Migration Inhibitory Factor Level in Sera of Patients with Alopecia Areata

Backgroundalopecia areata(AA) is a common recurrent non‐scarring type of hair loss. the pathogenesis of AA is still uncertain. The immune system has been implicated in its pathogenesis and certain immunomodulatory cytokines play a role in its development. Migration inhibitory factor(MIF) was reported to the first lymphokine which prevents the random migration of macrophages. A recent finding demonstrated that MIF innitiates inflammation and immune response by stimulating the secretion of several pro‐inflammatory cytokines. As regards skin diseases, MIF production by peripheral blood mononuclear cells has been reported to be markedly increased in patients with atopic dermatitis.The aim of the present work was to measure the serum MIF concentration in patients with AA and in health indivduals.Subjects and methodsThe present study was carried out on 30 patients with AA and 15 healthy controls. The serum level of MIF was measured by enzyme linked immunosorbent assay (ELISA).Resultsthe mean level of MIF in AA patients was 6.535ng/ml+3.51(mean+SD), while in healthy individuals was 1.89ng/ml+0.91(mean+SD)with statistical sinificant difference (p‐0.016).ConclusionMean serum MIF in patients with AA was higher than that in healthy subjects indicating that MIF has a role in the etiopathogenesis of AA

Climatic Factors Correlate with Innate Immune Response in Children with Dermatophagoides farinae-Induced Allergic Asthma

To determine the effect of climatic factors on immune markers in children with Dermatophagoides farinae induced asthma. Serum concentrations of macrophage migration inhibitory factor (MIF), eosinophil cationic protein (ECP) and D. farinae-specific immunoglobulin E (DF-sIgE), together with peripheral blood eosinophil counts, were measured in children with D. farinae induced (n = 75) or non-D. farinae-induced asthma (n = 17), and in healthy controls (n = 30). Mean temperature and relative humidity in the month before enrolment were calculated from meteorological data. MIF, ECP and eosinophil counts were significantly higher in children with D. farinae-induced asthma than in controls, but comparable with non-D. farinae-induced asthma. Children with D. farinae-induced asthma in a low temperature (< 16 °C) or low relative humidity (< 70%) climate had significantly lower DF-sIgE, MIF, ECP and eosinophil counts than those in a high temperature or high humidity climate. DF-sIgE correlated positively with MIF, ECP and eosinophil count in D. farinae-induced asthma. Temperature and humidity influenced MIF, ECP, eosinophil count and DF-sIgE in D. farinae-induced asthma. Understanding this relationship may provide new strategies for asthma prevention and treatment.

CD74 and macrophage migration inhibitory factor as therapeutic targets in gastric cancer.

To investigate the relationship and molecular features of CD74/macrophage migration inhibitory factor (MIF)/Toll-like receptor 4 (TLR4) in gastric cancer. CD74, MIF and TLR4 expression in the paraffin-embedded sections of gastric cancer from 120 patients were detected by immunohistochemical staining. Knock down of CD74 expression in gastric cancer cell line MKN-45 was performed by lentivirus transduction and detected by Western blotting. MKN-45 cell proliferation assay under the stimulants was measured by the cell counting kit 8 (CCK8) assay and MIF concentration in the culture medium was detected by enzyme-linked immunosorbent assay. Surface staining of CD74 in the MKN-45 cell line under the stimulation of lipopolysaccharide (LPS) was measured by flow cytometry. MIF, CD74 and TLR4 co-localization in the MKN-45 cell line was performed by the immunoprecipitation. CD74, MIF and TLR4 were found to be expressed in gastric cancer and increased significantly in the advanced stage, and were also associated with lymph node metastasis. Correlation analysis revealed that CD74 was positively correlated with MIF (r = 0.2367, P < 0.01) and both proteins were also associated with TLR4 (r = 0.4414, r = 0.5001, respectively, P < 0.01). LPS can significantly promote MKN-45 cell proliferation (3.027 ± 0.388 vs 4.201 ± 0.092, P < 0.05), induce MIF production (54.333 ± 2.906 pg/mL vs 29.667 ± 3.180 pg/mL, P < 0.01) and cell surface expression of CD74 (75.6% ± 4.046% vs 9.4% ± 0.964%, P < 0.01) at LPS concentration of 1 μg/mL compared to medium control. Knockdown of CD74 or using anti-CD74 and MIF antagonist ISO-1 significantly reduced LPS-induced MKN-45 cell proliferation (4.201 ± 0.092 vs 3.337 ± 0.087, 4.534 ± 0.222 vs 3.368 ± 0.290, 4.058 ± 0.292 vs 2.934 ± 0.197, respectively, P < 0.01). MIF, CD74 and TLR4 could co-localize in the MKN-45 cell line. Upregulation of MIF, CD74 and TLR4 are associated with increasing clinical stage and provide an opportunity as novel gastric cancer chemoprevention and/or treatment strategy.

Serum macrophage migration‐inhibitory factor as a diagnostic and prognostic biomarker for gastric cancer

This study aimed to determine the potential diagnostic value of migration-inhibitory factor (MIF) for gastric cancer in patients presenting with dyspepsia and its prognostic value for gastric cancer. A cohort of 97 patients with histologically confirmed gastric adenocarcinoma and 222 patients with dyspepsia were recruited. Enzyme-linked immunosorbent assay was used to measure serum MIF and carcinoembryonic antigen (CEA). The serum MIF concentrations were 6554.0 +/- 204.1 pg/mL and 1453.7 +/- 79.9 pg/mL, respectively, in gastric cancer patients and dyspeptic patients (P < .001). Serum MIF levels increased with the advancing gastric pathologies (P < .001). With the cutoff value of 3230 pg/mL, serum MIF had sensitivity, specificity, and accuracy of 83.5%, 92.3%, and 89.7%, respectively, in diagnosing gastric cancer, whereas the rates were 60.8%, 83.3%, and 76.5%, respectively, for serum CEA. Gastric cancer patients with serum MIF levels above 6600 pg/mL had a lower 5-year survival rate than those with serum MIF level below that level (P = .012). Higher serum CEA levels were also associated with poor survival. The prediction for 5-year survival was even better (P = .0001), using a combination of serum MIF and CEA. Serum MIF level, which correlates with gastric MIF expression, is a better molecular marker than CEA in diagnosing gastric cancer in patients presenting with dyspepsia. A combination of serum MIF and CEA predicts 5-year survival better than the individual test.

Up-regulated macrophage migration inhibitory factor protects apoptosis of dermal fibroblasts in patients with systemic sclerosis

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that has been demonstrated to regulate the apoptosis of several cell types. Dysregulated apoptosis of fibroblasts has been implicated in a variety of fibrotic diseases, including systemic sclerosis (SSc). In this study, we investigated the role of MIF in the apoptosis of dermal fibroblasts. The concentrations of MIF were measured in sera and in culture supernatants of peripheral blood mononuclear cells (PBMCs) and dermal fibroblasts by enzyme-linked immunosorbent assay. The degree of apoptosis was determined by colorimetric assay, and signalling pathways were examined by Western blot. The results showed that serum levels of MIF were significantly higher in patients with SSc (n = 47) than in healthy controls (n = 56). Stimulation of PBMCs by anti-CD3 and anti-CD28 increased the production of MIF by fourfold over the constitutive levels. SSc dermal fibroblasts produced higher amounts of MIF than normal dermal fibroblasts. When treated with sodium nitroprusside (SNP), SSc dermal fibroblasts showed a lower degree of apoptosis compared with normal dermal fibroblasts. Exogenous MIF (1-100 ng/ml) inhibited SNP-induced apoptosis of dermal fibroblasts dose-dependently. Both extracellular regulated kinase (ERK) inhibitor (PD98059) and protein kinase B (Akt) inhibitor (LY294002) almost completely blocked the inhibitory effect of MIF on apoptosis. Furthermore, MIF increased the expression of Bcl-2, phospho-ERK and phospho-Akt activity in dermal fibroblasts. Taken together, our data suggest that MIF released by activated T cells and dermal fibroblasts decreases the apoptosis of dermal fibroblasts through activation of ERK, Akt and Bcl-2 signalling pathways, which might be associated with excessive fibrosis in SSc.

Similar cytokine responses and degrees of anemia in patients with Plasmodium falciparum and Plasmodium vivax infections in the Brazilian Amazon region.

The mechanisms of malarial anemia induction are poorly understood, but cytokines and autoantibodies are considered to play important roles. This work aimed at evaluating the degree of anemia and the plasmatic profile of the cytokines tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-12 (IL-12), migration inhibitory factor (MIF), and IL-10 and the monocyte chemotactic protein-1 (MCP-1) chemokine, as well as evaluating the presence of antibodies directed to components of the normal erythrocyte membrane and to cardiolipin in individuals with malaria from the Brazilian Amazon. No difference was observed in the frequency of anemia between patients infected by Plasmodium vivax and those infected by Plasmodium falciparum, and there was no relationship between the levels of parasitemia and the manifestations of anemia in P. vivax and P. falciparum patients. Significant increases in the concentrations of TNF-alpha, IFN-gamma, MIF, and MCP-1 were observed in patients with P. falciparum and P. vivax malaria, whereas the concentrations of IL-10 was increased only in patients with P. vivax infection. Higher concentrations of IL-12 and IL-10 were observed in the P. falciparum anemic patients, while for TNF-alpha this profile was observed in the nonanemic ones. P. vivax-infected and P. falciparum-infected patients with positive immunoglobulin M (IgM) or IgM and IgG responses, respectively, against blood-stage forms of the parasites had significantly lower hemoglobin levels than did those with negative responses. There was no correlation between the presence of anti-erythrocyte and anti-cardiolipin antibodies and the presence or intensity of the anemia. Our data suggest that in areas of low endemicity and unstable transmission of malaria, P. vivax and P. falciparum infections present similar characteristics in terms of the induction of anemia and cytokine responses.

Serum macrophage migration inhibitory factor (MIF) in the intercritical phase of hereditary periodic fevers and its relationship with the MIF‐173G/C polymorphism

Objectives: To examine the association of the −173 single‐nucleotide G/C polymorphism of the macrophage migration inhibitory factor gene (MIF) and serum macrophage migration inhibitory factor (MIF) concentrations in a group of Italian patients with hereditary periodic fevers (HPF), tested during a symptom‐free phase of their disease.Methods: Genomic DNA for MIF and serum MIF were evaluated in 22 patients with HPF and compared with healthy controls of the same ethnic group. The MIF‐173G/C polymorphism was genotyped using polymerase chain reaction (PCR) and visualized by ethidium bromide staining. Serum MIF levels were measured by enzyme‐linked immunosorbent assay (ELISA).Results:MIF‐173*C allele frequency and MIF serum concentrations were significantly higher in patients with HPF than in controls, with no statistically significant difference between familial Mediterranean fever (FMF) and hyperimmunoglobulinaemia D/periodic fever syndrome (HIDS) and no correlation with specific MIF genotypes.Conclusions: The MIF‐173*C allele was found more frequently in patients with HPF than in controls and MIF serum concentrations were considerably elevated in attack‐free phases, suggesting a persistent state of subclinical cytokine activation with MIF involvement in the autoinflammatory cascade.